VITAMIN K
A. History. Henrick Dam (1929), a Danish
investigator, found that newly-hatched chicks, fed on artificial diets, develop hemorrhage, a fatal disease characterized by prolonged blood-clotting period. The term vitamin K (K for Danish koagulations) was then proposed by Dam (1934) himself to designate the active factor which cured or prevented this disease. On account of its blood-clotting power, it is also called as antihemorrhagic factor or coagulation vitamin. Of the 2 naturally-occurring forms of this vitamin, vitamin K1 was first isolated by Dametal from alfalfa in 1939 and the other
form, vitamin K2 from fish meal by Doisy et al, also in 1939.
B. Occurrence. Vitamin K1 occurs in green vegetables like spinach, alfalfa, cabbage etc.
Fruits and cereals are poor sources. Vitamin K2 is found in some intestinal bacteria. A rich source
of K2 is putrefied fish meal. Their relative biologic potencies are :
the naphthoquinone ring. It is a phytol radical in vitamin K1 (C31H46O2) and a difarnesyl radical in vitamin K2 (C41H56O2). Vitamin K1, found in plants, has 4 isoprene units in its side chain whereas vitamin K2, found in animals, contains in its side 6 isoprene units, each with a double bond.
Analogues— The various analogues of naphthoquinone, however, have also been shown to possess vitamin K activity for animals. This is due to their structural resemblance. The common examples are menadione and phthiocol (in Fig.).
Menadione, which is sometimes referred to as vitamin K3, is twice as potent as vitamin K1. It is soluble in oil, sparingly so in water and is not oxidized in air when protected from light. Its diphosphate ester is water-soluble and is widely used clinically.
D. Properties. Vitamin K1 is a yellow viscid oil but vitamin K2 is a yellowish crystalline
solid. It is sensitive to light and is, therefore, kept in dark bottles. It is destroyed by irradiation,
strong acids, alkalies and oxidizing agents.
E. Metabolism. Vitamin K plays an essential role in the biosynthesis of prothrombin— a
blood plasma protein needed in the process of blood clotting and produced in liver. The process
of blood coagulation may be summarized as below.
[Note the role of vitamin K in the synthesis of prothrombin which is a precursor of thrombin, the latter has dual function of (a) hydrolysing fibrinogen to fibrin and (b) activating fibrinase of FSF, which brings about
clotting.]
The formation of the blood clot (refer Fig. ) is caused by the enzymic hydrolysis of the soluble plasma protein, fibrinogen to the insoluble protein, fibrin and fibrinopeptides. This transformation is catalyzed by an enzyme, thrombin. Thrombin itself is not present in the blood but is produced from its precursor, prothrombin in the presence of Ca2+ ions and another protein called thromboplastin ( = thrombokinase). In the next step, fibrin forms soft, fibrous networks (or soft clots). Then in the presence of Ca2+, thrombin activates fibrinase, an enzyme precursor found in blood plasma. Fibrinase is also known as fibrin-stabilizing factor (FSF). Finally, fibrous networks of fibrin link with each other under the influence of activated FSF to produce cross-linked fibrin (or hard clots).
The vitamins K are fat-soluble and are absorbed only in the presence of bile. As a result, the absorption occurs in the upper portion of the small intestine where bile salts are present. The avitaminosis K may occur where bile is prevented from entering the intestinal tract. This is true for most of the fat-soluble vitamins but is, in particular, important in the case of vitamin K because of its blood clotting action.
Like vitamin E and coenzyme Q, the vitamin K has also been ascribed a role in electron transport system (ETS) and oxidative phosphorylation in mitochondria. The vitamin K1 and K2 both activate electron transport in the succinate oxidase of cardiac muscle preparations that have been made inactive by treating with isooctane. The bacterial extracts or liver mitochondria, when Antagonists irradiated, require vitamin K for oxidative phosphorylation. This suggests a possible role of vitamin K in oxidative phosphorylation. The specific site of action is believed to occur between NADH and cytochrome b. It has been suggested that a phosphate ester of vitamin K, upon oxidation, transfers phosphate to ADP to form ATP.
Antagonists— Two antagonists of vitamin K are dicumarol and warfarin (inFig.) ; both
antagonists prevent blood clotting. Dicumarol was first isolated from mouldy clover hay. It is often given to patients, who have suffered heart attacks caused by blood clots, as as preventive measure against further clotting in the blood vessels. Warfarin (name derived from the initials of the Wisconsin alumni Research Foundation, which sponsored the research on the compound) is a synthetic analogue of vitamin K. It is extremely poisonous to rats, causing death by internal bleeding. Ironically, this potent rodenticide is also a valuable anticoagulant drug for the treatment of human patients in whom excessive bleeding is dangerous— surgical patients and victims of coronary thrombosis.
Note that both dicumarol and warfarin lack an isoprenoid side chain.
In 1988, by introducing the antioxidant vitamin E, David Gershon and his colleagues at the Technion–Israel Institute of Technology, have succeeded in reducing cell damage and increasing the life span of nematode worms. The damage body cells sustain is due to oxidation, an underlying mechanism of ageing, which also damages the disposal system. Paradoxically, the oxygen we depend on for life is a source of our age-associated decline in function. Similar researches conducted on humans might shed light on how to intervene and retard ageing in them.
F. Deficiency. Deficiency of vitamin K causes loss of blood-clotting power. The infants
may also show signs of vitamin K deficiency by developing hemorrhage. This disease persists
by the time the bacteria develop in the intestine. Administration of this vitamin to pregnant
mothers before parturition decreases the onset of this disease. In man, however, avitaminosis K
results in steatorrhea with diminished intestinal absorption of lipids.
In general, vitamin K deficiency is rarely found in higher animals as this is provided by food and also synthesized by intestinal bacteria.
G. Human requirements. There is seldom a lack of sufficient vitamin K in human beings. As such, no standard requirement has been set.
investigator, found that newly-hatched chicks, fed on artificial diets, develop hemorrhage, a fatal disease characterized by prolonged blood-clotting period. The term vitamin K (K for Danish koagulations) was then proposed by Dam (1934) himself to designate the active factor which cured or prevented this disease. On account of its blood-clotting power, it is also called as antihemorrhagic factor or coagulation vitamin. Of the 2 naturally-occurring forms of this vitamin, vitamin K1 was first isolated by Dametal from alfalfa in 1939 and the other
form, vitamin K2 from fish meal by Doisy et al, also in 1939.
B. Occurrence. Vitamin K1 occurs in green vegetables like spinach, alfalfa, cabbage etc.
Fruits and cereals are poor sources. Vitamin K2 is found in some intestinal bacteria. A rich source
of K2 is putrefied fish meal. Their relative biologic potencies are :
- vitamin K1—100
- vitamin K2—80
the naphthoquinone ring. It is a phytol radical in vitamin K1 (C31H46O2) and a difarnesyl radical in vitamin K2 (C41H56O2). Vitamin K1, found in plants, has 4 isoprene units in its side chain whereas vitamin K2, found in animals, contains in its side 6 isoprene units, each with a double bond.Analogues— The various analogues of naphthoquinone, however, have also been shown to possess vitamin K activity for animals. This is due to their structural resemblance. The common examples are menadione and phthiocol (in Fig.).
Menadione, which is sometimes referred to as vitamin K3, is twice as potent as vitamin K1. It is soluble in oil, sparingly so in water and is not oxidized in air when protected from light. Its diphosphate ester is water-soluble and is widely used clinically.
D. Properties. Vitamin K1 is a yellow viscid oil but vitamin K2 is a yellowish crystalline
solid. It is sensitive to light and is, therefore, kept in dark bottles. It is destroyed by irradiation,
strong acids, alkalies and oxidizing agents.
E. Metabolism. Vitamin K plays an essential role in the biosynthesis of prothrombin— a
blood plasma protein needed in the process of blood clotting and produced in liver. The process
of blood coagulation may be summarized as below.
[Note the role of vitamin K in the synthesis of prothrombin which is a precursor of thrombin, the latter has dual function of (a) hydrolysing fibrinogen to fibrin and (b) activating fibrinase of FSF, which brings about
clotting.]
The formation of the blood clot (refer Fig. ) is caused by the enzymic hydrolysis of the soluble plasma protein, fibrinogen to the insoluble protein, fibrin and fibrinopeptides. This transformation is catalyzed by an enzyme, thrombin. Thrombin itself is not present in the blood but is produced from its precursor, prothrombin in the presence of Ca2+ ions and another protein called thromboplastin ( = thrombokinase). In the next step, fibrin forms soft, fibrous networks (or soft clots). Then in the presence of Ca2+, thrombin activates fibrinase, an enzyme precursor found in blood plasma. Fibrinase is also known as fibrin-stabilizing factor (FSF). Finally, fibrous networks of fibrin link with each other under the influence of activated FSF to produce cross-linked fibrin (or hard clots).
The vitamins K are fat-soluble and are absorbed only in the presence of bile. As a result, the absorption occurs in the upper portion of the small intestine where bile salts are present. The avitaminosis K may occur where bile is prevented from entering the intestinal tract. This is true for most of the fat-soluble vitamins but is, in particular, important in the case of vitamin K because of its blood clotting action.
Like vitamin E and coenzyme Q, the vitamin K has also been ascribed a role in electron transport system (ETS) and oxidative phosphorylation in mitochondria. The vitamin K1 and K2 both activate electron transport in the succinate oxidase of cardiac muscle preparations that have been made inactive by treating with isooctane. The bacterial extracts or liver mitochondria, when Antagonists irradiated, require vitamin K for oxidative phosphorylation. This suggests a possible role of vitamin K in oxidative phosphorylation. The specific site of action is believed to occur between NADH and cytochrome b. It has been suggested that a phosphate ester of vitamin K, upon oxidation, transfers phosphate to ADP to form ATP.
Antagonists— Two antagonists of vitamin K are dicumarol and warfarin (inFig.) ; both
antagonists prevent blood clotting. Dicumarol was first isolated from mouldy clover hay. It is often given to patients, who have suffered heart attacks caused by blood clots, as as preventive measure against further clotting in the blood vessels. Warfarin (name derived from the initials of the Wisconsin alumni Research Foundation, which sponsored the research on the compound) is a synthetic analogue of vitamin K. It is extremely poisonous to rats, causing death by internal bleeding. Ironically, this potent rodenticide is also a valuable anticoagulant drug for the treatment of human patients in whom excessive bleeding is dangerous— surgical patients and victims of coronary thrombosis.
Note that both dicumarol and warfarin lack an isoprenoid side chain.
In 1988, by introducing the antioxidant vitamin E, David Gershon and his colleagues at the Technion–Israel Institute of Technology, have succeeded in reducing cell damage and increasing the life span of nematode worms. The damage body cells sustain is due to oxidation, an underlying mechanism of ageing, which also damages the disposal system. Paradoxically, the oxygen we depend on for life is a source of our age-associated decline in function. Similar researches conducted on humans might shed light on how to intervene and retard ageing in them.
F. Deficiency. Deficiency of vitamin K causes loss of blood-clotting power. The infants
may also show signs of vitamin K deficiency by developing hemorrhage. This disease persists
by the time the bacteria develop in the intestine. Administration of this vitamin to pregnant
mothers before parturition decreases the onset of this disease. In man, however, avitaminosis K
results in steatorrhea with diminished intestinal absorption of lipids.
In general, vitamin K deficiency is rarely found in higher animals as this is provided by food and also synthesized by intestinal bacteria.
G. Human requirements. There is seldom a lack of sufficient vitamin K in human beings. As such, no standard requirement has been set.
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